scholarly journals Lactobacillus rhamnosus GR-1 Ameliorates Escherichia coli-Induced Inflammation and Cell Damage via Attenuation of ASC-Independent NLRP3 Inflammasome Activation

2015 ◽  
Vol 82 (4) ◽  
pp. 1173-1182 ◽  
Author(s):  
Qiong Wu ◽  
Ming-Chao Liu ◽  
Jun Yang ◽  
Jiu-Feng Wang ◽  
Yao-Hong Zhu
Keyword(s):  
Escherichia Coli ◽  
Mrna Expression ◽  
Nlrp3 Inflammasome ◽  
Cell Damage ◽  
Lactobacillus Rhamnosus ◽  
Adaptor Protein ◽  
Inflammasome Activation ◽  
Content Type ◽  
E Coli ◽  
Nlrp3 Inflammasome Activation

ABSTRACTEscherichia coliis a major environmental pathogen causing bovine mastitis, which leads to mammary tissue damage and cell death. We explored the effects of the probioticLactobacillus rhamnosusGR-1 on amelioratingE. coli-induced inflammation and cell damage in primary bovine mammary epithelial cells (BMECs). Increased Toll-like receptor 4 (TLR4), NOD1, and NOD2 mRNA expression was observed followingE. colichallenge, but this increase was attenuated byL. rhamnosusGR-1 pretreatment. Immunofluorescence and Western blot analyses revealed thatL. rhamnosusGR-1 pretreatment decreased theE. coli-induced increases in the expression of the NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3) and the serine protease caspase 1. However, expression of the adaptor protein apoptosis-associated speck-like protein (ASC, encoded by thePycardgene) was decreased duringE. coliinfection, even withL. rhamnosusGR-1 pretreatment. Pretreatment withL. rhamnosusGR-1 counteracted theE. coli-induced increases in interleukin-1β (IL-1β), -6, -8, and -18 and tumor necrosis factor alpha mRNA expression but upregulated IL-10 mRNA expression. Our data indicate thatL. rhamnosusGR-1 reduces the adhesion ofE. colito BMECs, subsequently amelioratingE. coli-induced disruption of cellular morphology and ultrastructure and limiting detrimental inflammatory responses, partly via promoting TLR2 and NOD1 synergism and attenuating ASC-independent NLRP3 inflammasome activation. Although the residual pathogenic activity ofL. rhamnosus, the dosage regimen, and the means of probiotic supplementation in cattle remain undefined, our data enhance our understanding of the mechanism of action of this candidate probiotic, allowing for development of specific probiotic-based therapies and strategies for preventing pathogenic infection of the bovine mammary gland.

scholarly journals Lactobacillus rhamnosus GR-1 Prevents Escherichia coli-Induced Apoptosis Through PINK1/Parkin-Mediated Mitophagy in Bovine Mastitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanan Li ◽  
Yaohong Zhu ◽  
Bingxin Chu ◽  
Ning Liu ◽  
Shiyan Chen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
T Cells ◽  
Nlrp3 Inflammasome ◽  
Bovine Mastitis ◽  
Lactobacillus Rhamnosus ◽  
Inflammasome Activation ◽  
Ros Production ◽  
E Coli ◽  
Nlrp3 Inflammasome Activation ◽  
Induced Apoptosis

Escherichia coli is one of the most important pathogens that cause clinical mastitis in dairy cattle worldwide and lead to severe economic losses. Antibiotics are often used to treat this inflammatory disease; however, antimicrobial resistance and environmental pollution cannot be ignored. Probiotic is the best alternative; however, its mechanisms of action to prevent mastitis remain unclear. Moreover, the role of probiotics in regulating mitophagy, a selective autophagy that maintains mitochondrial quality, needs to be explored. E. coli infection induced NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3) inflammasome assembly, Caspase-1 activation, and apoptosis in MAC-T cells. Infection also resulted in mitochondrial damage and subsequent increase in reactive oxygen species (ROS) production. Moreover, inhibition of ROS release by scavenger N-acetyl-L-cysteine (NAC) abrogated the importance of ROS in NLRP3 assembly and apoptosis in MAC-T cells. Pretreatment with Lactobacillus rhamnosus GR-1 (LGR-1), a probiotic, alleviated E. coli-induced NLRP3 inflammasome activation and apoptosis via ROS inhibition. Besides, E. coli infection inhibited mitophagy while LGR-1 pretreatment augmented PINK1/Parkin–mediated mitophagy activation, which further blocked ROS generation. To explore the effect of LGR-1 in vivo, a mouse mastitis model was established. The results showed that LGR-1 pretreatment had preventive and protective effects on E. coli induced mastitis, and could reduce cytokines levels such as IL-1β and TNF-α. In accordance with the results in vitro, E. coli can inhibit mitophagy and activate NLRP3 inflammasome and apoptosis, while LGR-1 can weaken the effect of E. coli. Taken together, our data indicated that LGR-1 pretreatment induced PINK1/Parkin-mediated mitophagy that eliminated damaged mitochondria and reduced ROS production and NLRP3 inflammasome activation, which subsequently decreased E. coli-induced apoptosis. To conclude, our study suggests that therapeutic strategies aiming at the upregulation of mitophagy under E. coli-induced mastitis may preserve mitochondrial function and provide theoretical support for the application of probiotics in bovine mastitis.

scholarly journals A novel function of NLRP3 independent of inflammasome as a key transcription factor of IL-33 in epithelial cells of atopic dermatitis

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Jie Zheng ◽  
Lu Yao ◽  
Yijing Zhou ◽  
Xiaoqun Gu ◽  
Can Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Atopic Dermatitis ◽  
Epithelial Cells ◽  
Mrna Expression ◽  
Nlrp3 Inflammasome ◽  
Myeloid Cells ◽  
Pathological Process ◽  
Inflammasome Activation ◽  
Mice Model ◽  
Nlrp3 Inflammasome Activation

AbstractAtopic dermatitis (AD) is a common chronic pruritic inflammatory skin disorder characterized by recurrent eczematous lesions. Interleukin (IL)−33, a cytokine of the IL-1 family, was found to play an important role in the pathogenesis of AD. As a key component of the inflammasome, NLRP3 has been mostly described in myeloid cells that to mediate inflammasome activation conducted proinflammatory cytokine production of the IL-1 family. However, the role of NLRP3 inflammasome in the pathogenesis of AD, as well as IL-33 processing are highly controversial. Whether NLRP3 can mediate IL-33 expression and secretion independently of the inflammasome in the epithelium of AD has remained unclear. In this article, we found the mRNA expression of Il33 and Nlrp3 were notably increased in the lesional skin of AD patients compared to healthy controls. We then found a significant positive correlation between the expression of Nlrp3 and Il33 in the epithelium of MC903-mediated AD mice model, but no changes were observed for Il36α, Il36γ, Il1β, or Il18 mRNA expression, as well as IL-1β or IL-18 production. Overexpression of NLRP3 in human immortalized epithelial cells increased IL-33 expression, whereas siRNA targeting NLRP3 abolished IL-33 expression. In addition, inhibition of NLRP3 inflammasome activation or caspase-1 activity with MCC950 or VX-765 showed no effect on the expression and secretion of IL-33 in AD mice. Unlike myeloid cells, NLRP3 predominantly located in the nucleus of epithelial cells, which could directly bind to Il33 specific-promoters and transactivate it through an interaction with transcription factor IRF4. Furthermore, NLRP3 deficient mice exhibited a significant alleviated epidermis inflammation and decreased mRNA expression and secretion of IL-33 in MC903-mediated AD mice without interfering with TSLP and IL-1β production. Our results demonstrate a novel ability of NLRP3 to function as a crucial transcription factor of IL-33 in epithelium independently of inflammasome that to mediate the pathological process of AD.

scholarly journals ADP-Ribosylation of NLRP3 by Mycoplasma pneumoniae CARDS Toxin Regulates Inflammasome Activity

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Santanu Bose ◽  
Jesus A. Segovia ◽  
Sudha R. Somarajan ◽  
Te-Hung Chang ◽  
T. R. Kannan ◽  
...  
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Proinflammatory Cytokines ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Content Type ◽  
Adp Ribosylation ◽  
Protein Toxin ◽  
Nlrp3 Inflammasome Activation ◽  
Adp Ribosyltransferase ◽  
Cards Toxin

ABSTRACTThe inflammasome is a major regulator of inflammation through its activation of procaspase-1, which cleaves prointerleukin-1β (pro-IL-1β) into its mature form. IL-1β is a critical proinflammatory cytokine that dictates the severity of inflammation associated with a wide spectrum of inflammatory diseases. NLRP3 is a key component of the inflammasome complex, and multiple signals and stimuli trigger formation of the NLRP3 inflammasome complex. In the current study, we uncovered a yet unknown mechanism of NLRP3 inflammasome activation by a pathogen-derived factor. We show that the unique bacterial ADP-ribosylating and vacuolating toxin produced byMycoplasma pneumoniaeand designated community-acquired respiratory distress syndrome (CARDS) toxin activates the NLRP3 inflammasome by colocalizing with the NLRP3 inflammasome and catalyzing the ADP-ribosylation of NLRP3. Mutant full-length CARDS toxin lacking ADP-ribosyltransferase (ADPRT) activity and truncated CARDS toxins unable to bind to macrophages and be internalized failed to activate the NLRP3 inflammasome. These studies demonstrate that CARDS toxin-mediated ADP-ribosylation constitutes an important posttranslational modification of NLRP3, that ADPRT activity of CARDS toxin is essential for NLRP3 inflammasome activation, and that posttranslational ADPRT-mediated modification of the inflammasome is a newly discovered mechanism for inflammasome activation with subsequent release of IL-1β and associated pathologies.IMPORTANCEInflammation is a fundamental innate immune response to environmental factors, including infections. The inflammasome represents a multiprotein complex that regulates inflammation via its ability to activate specific proinflammatory cytokines, resulting in an effective host protective response. However, excessive release of proinflammatory cytokines can occur following infection that skews the host response to “hyperinflammation” with exaggerated tissue damage.Mycoplasma pneumoniae, a common bacterial airway pathogen, possesses a unique protein toxin with ADP-ribosyltransferase and vacuolating properties capable of reproducing the robust inflammation and cytopathology associated with mycoplasma infection. Here, we show that the toxin uniquely activates the NLRP3 inflammasome by colocalizing with and ADP-ribosylating NLRP3, possibly leading to “hyperinflammation” and thus uncovering a novel target for therapeutic intervention.

scholarly journals Uropathogenic Escherichia coli strain CFT073 disrupts NLRP3 inflammasome activation

2016 ◽  
Vol 126 (7) ◽  
pp. 2425-2436 ◽  
Author(s):  
Anna Waldhuber ◽  
Manoj Puthia ◽  
Andreas Wieser ◽  
Christine Cirl ◽  
Susanne Dürr ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Nlrp3 Inflammasome ◽  
Coli Strain ◽  
Uropathogenic Escherichia Coli ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Strain Cft073

scholarly journals NLRP3 inflammasome in endothelial dysfunction

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Baochen Bai ◽  
Yanyan Yang ◽  
Qi Wang ◽  
Min Li ◽  
Chao Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Protein Complexes ◽  
Cell Damage ◽  
Inflammasome Activation ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation ◽  
Clinical Drugs

Abstract Inflammasomes are a class of cytosolic protein complexes. They act as cytosolic innate immune signal receptors to sense pathogens and initiate inflammatory responses under physiological and pathological conditions. The NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18, which are mediated by caspase-1, and secretes mature forms of these mediators from cells to promote the further inflammatory process and oxidative stress. Simultaneously, cells undergo pro-inflammatory programmed cell death, termed pyroptosis. The danger signals for activating NLRP3 inflammasome are very extensive, especially reactive oxygen species (ROS), which act as an intermediate trigger to activate NLRP3 inflammasome, exacerbating subsequent inflammatory cascades and cell damage. Vascular endothelium at the site of inflammation is actively involved in the regulation of inflammation progression with important implications for cardiovascular homeostasis as a dynamically adaptable interface. Endothelial dysfunction is a hallmark and predictor for cardiovascular ailments or adverse cardiovascular events, such as coronary artery disease, diabetes mellitus, hypertension, and hypercholesterolemia. The loss of proper endothelial function may lead to tissue swelling, chronic inflammation, and the formation of thrombi. As such, elimination of endothelial cell inflammation or activation is of clinical relevance. In this review, we provided a comprehensive perspective on the pivotal role of NLRP3 inflammasome activation in aggravating oxidative stress and endothelial dysfunction and the possible underlying mechanisms. Furthermore, we highlighted the contribution of noncoding RNAs to NLRP3 inflammasome activation-associated endothelial dysfunction, and outlined potential clinical drugs targeting NLRP3 inflammasome involved in endothelial dysfunction. Collectively, this summary provides recent developments and perspectives on how NLRP3 inflammasome interferes with endothelial dysfunction and the potential research value of NLRP3 inflammasome as a potential mediator of endothelial dysfunction.

scholarly journals α-Hemolysin of uropathogenic E. coli regulates NLRP3 inflammasome activation and mitochondrial dysfunction in THP-1 macrophages

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vivek Verma ◽  
Parveen Kumar ◽  
Surbhi Gupta ◽  
Sonal Yadav ◽  
Rakesh Singh Dhanda ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
E Coli ◽  
Nlrp3 Inflammasome Activation

scholarly journals Lactobacillus johnsonii L531 Ameliorates Escherichia coli-Induced Cell Damage via Inhibiting NLRP3 Inflammasome Activity and Promoting ATG5/ATG16L1-Mediated Autophagy in Porcine Mammary Epithelial Cells

2020 ◽  
Vol 7 (3) ◽  
pp. 112
Author(s):  
Yun-Jing Zou ◽  
Jia-Jia Xu ◽  
Xue Wang ◽  
Yao-Hong Zhu ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Nlrp3 Inflammasome ◽  
Mammary Epithelial Cells ◽  
Cell Damage ◽  
Mammary Epithelial ◽  
Mammary Tissue ◽  
Lactobacillus Johnsonii ◽  
E Coli ◽  
Inflammasome Activity

Escherichia coli (E. coli), a main mastitis-causing pathogen in sows, leads to mammary tissue damage. Here, we explored the effects of Lactobacillus johnsonii L531 on attenuating E. coli-induced inflammatory damage in porcine mammary epithelial cells (PMECs). L. johnsonii L531 pretreatment reduced E. coli adhesion to PMECs by competitive exclusion and the production of inhibitory factors and decreased E. coli-induced destruction of cellular morphology and ultrastructure. E. coli induced activation of NLRP3 inflammasome associated with increased expression of NLRP3, ASC, and cleaved caspase-1, however, L. johnsonii L531 inhibited E. coli-induced activation of NLRP3 inflammasome. Up-regulation of interleukin (Il)-1β, Il-6, Il-8, Il-18, tumor necrosis factor alpha, and chemokine Cxcl2 expression after E. coli infection was attenuated by L. johnsonii L531. E. coli infection inhibited autophagy, whereas L. johnsonii L531 reversed the inhibitory effect of E. coli on autophagy by decreasing the expression of autophagic receptor SQSTM1/p62 and increasing the expression of autophagy-related proteins ATG5, ATG16L1, and light chain 3 protein by Western blotting analysis. Our findings suggest that L. johnsonii L531 pretreatment restricts NLRP3 inflammasome activity and induces autophagy through promoting ATG5/ATG16L1-mediated autophagy, thereby protecting against E. coli-induced inflammation and cell damage in PMECs.

scholarly journals Pretreatment with a Heat-Killed Probiotic Modulates the NLRP3 Inflammasome and Attenuates Colitis-Associated Colorectal Cancer in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 516 ◽  
Author(s):  
I-Che Chung ◽  
Chun-Nan OuYang ◽  
Sheng-Ning Yuan ◽  
Hsin-Chung Lin ◽  
Kuo-Yang Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Nlrp3 Inflammasome ◽  
Intestinal Inflammation ◽  
Inflammasome Activation ◽  
E Coli ◽  
Nlrp3 Inflammasome Activation ◽  
Safe Strategy ◽  
Inflammatory Bowel ◽  
Fecal Content

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Inflammation contributes to cancer development and inflammatory bowel disease is an important risk factor for CRC. The aim of this study is to assess whether a widely used probiotic Enterococcus faecalis can modulate the NLRP3 inflammasome and protect against colitis and colitis-associated CRC. We studied the effect of heat-killed cells of E. faecalis on NLRP3 inflammasome activation in THP-1-derived macrophages. Pretreatment of E. faecalis or NLRP3 siRNA can inhibit NLRP3 inflammasome activation in macrophages in response to fecal content or commensal microbes, P. mirabilis or E. coli, according to the reduction of caspase-1 activation and IL-1β maturation. Mechanistically, E. faecalis attenuates the phagocytosis that is required for the full activation of the NLRP3 inflammasome. In in vivo mouse experiments, E. faecalis can ameliorate the severity of intestinal inflammation and thereby protect mice from dextran sodium sulfate (DSS)-induced colitis and the formation of CRC in wild type mice. On the other hand, E. faecalis cannot prevent DSS-induced colitis in NLRP3 knockout mice. Our findings indicate that application of the inactivated probiotic, E. faecalis, may be a useful and safe strategy for attenuation of NLRP3-mediated colitis and inflammation-associated colon carcinogenesis.

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